Method for treating inflammatory diseases by administering a thrombin inhibitor

Abstract

The invention is a method for treating an inflammatory disease in a patient which comprises treating the patient with a composition comprising a thrombin inhibitor. Such diseases include but are not limited to nephritis, systemic lupus erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis. In one class of the method, the thrombin inhibitor is selected from the group consisting of 3-(2-phenylethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)-2-pyrazinone, N'-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide, and 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)-2-pyridinone or a pharmaceutically acceptable salt thereof.The invention is also a method for treating an inflammatory disease in a patient which comprises treating the patient with a composition comprising a thrombin inhibitor and an NSAID, e.g., a COX-2 inhibitor. Such diseases include but are not limited to nephritis, systemic lupus, erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis. In one class of the method, the thrombin inhibitor is selected from the group consisting of 3-(2-phenylethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-carboxamidomethylpyridinyl)-2-pyrazinone, N'-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide, and 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)-2-pyridinone or a pharmaceutically acceptable salt thereof and the COX-2 inhibitor is 3-phenyl-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone or a pharmaceutically acceptable salt thereof.

What is claimed is:  
     
       1. A method for treating a chronic inflammatory disease in a patient which comprises treating the patient with an oral composition comprising a thrombin inhibitor wherein the thrombin inhibitor is selected from the group consisting of 3-(2-phenylethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-carboxamidomethylpyridinyl)-2-pyrazinone, N′-[[1-(Aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide, and 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethyl-pyridinyl)-2-pyridinone or a pharmaceutically acceptable salt thereof. 
     
     
       2. A method for treating an inflammatory disease in a patient which comprises treating the patient with an oral composition comprising a thrombin inhibitor and a COX-2 inhibitor. 
     
     
       3. A method of claim  2  wherein the inflammatory disease is selected from the group consisting of nephritis, systemic lupus erythematosus, rheumatoid arthritis, glomerulonephritis, and sarcoidosis. 
     
     
       4. A method of claim  2  wherein the thrombin inhibitor is selected from the group consisting of 3-(2-phenylethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-carboxamidomethylpyridinyl)-2-pyrazinone, N′-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide, and 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylenecarboxamidomethylpyridinyl)-2-pyridinone. 
     
     
       5. A method of claim  4  wherein the COX-2 inhibitor is 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone or a pharmaceutically acceptable salt thereof. 
     
     
       6. A method of claim  4  wherein the COX-2 inhibitor is 3-phenyl-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone or a pharmaceutically acceptable salt thereof. 
     
     
       7. A method for inhibiting secondary chronic inflammation in a patient developing inflammation at a primary site which comprises treating the patient with a composition comprising an oral thrombin inhibitor.